Beta-amyloid, which acts in the brain, is known to cause diseases, including Alzheimer's disease, dementia such as vascular dementia, alcoholic dementia and dementia with Lewy bodies, Parkinson's disease, Huntington's disease, and inflammation of the brain (Irvine G B, El-Agnaf O M, Shankar G M, Walsh D M. “Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases” Mol Med. 2008; 14(7-8):451-64, etc.). In particular, Alzheimer's disease (AD) is the most common degenerative brain disease that causes dementia, accounting for 55-70% of all dementia.
Most of the drugs currently developed for dementia are acetylcholinesterase inhibitors that inhibit the degradation of acetylcholine, which is a neurotransmitter that is very important for memory function (U.S. Pat. No. 4,895,841, etc.). The acetylcholinesterase inhibitors focus on symptom relief rather than eliminating the cause thereof. Major side effects of these drugs include hyperactivity of the parasympathetic nervous system owing to excessive increase of acetylcholine, resulting in adverse digestive and neuropsychiatric events such as severe diarrhea, nausea, vomiting, depression, anxiety, insomnia, headaches, and the like. These drugs are difficult to use as practical therapeutic agents for Alzheimer's disease.
Meanwhile, peptides comprising the specific amino acid sequence (DAEF) are known as neuroprotective peptides that inhibit beta-amyloid-induced neuronal cytotoxicity (International Patent Publication No. WO 2006/031330 A2). Such peptides are known only to reduce or prevent beta-amyloid-induced effects such as tau protein phosphorylation or neuronal cell death.
Furthermore, since such a neuroprotective peptide needs to pass through a blood-brain barrier (BBB) in order to exhibit effects in the brain, additional means for entry into the brain (e.g., a catheter inserted by neurosurgery, etc.) has to be applied, which is considered difficult.
Accordingly, there is a need to develop drugs that may be more easily applied with the goal of inhibiting the intracerebral action of beta-amyloid.